Cardiac fibrosis is the underlying cause for the so-called diastolic dysfunction. Cardiac fibrosis is a process of "scarring" that results in increased stiffness of the cardiac tissue. Thus, relaxation (diastole) of the heart is disturbed, and the filling of the heart impaired. Until now, specific treatment to target the progression of cardiac fibrosis is not yet available. Fibrosis is considered to follow similar pathways in distinct tissues such as the heart, kidney, lung, skin or liver. Recent studies in the kidney demonstrated that "epithelial-mesenchymal- transition" (EMT) plays an important role in the progression of fibrosis. EMT is defined as a process in which epithelial cells differentiate into activated fibroblasts. As the endocardial cushion, which consists of mesenchymal cells, evolves via EMT from cells from the endocardium during heart development (regulated by BMPs), we hypothesized that endocardial cells could transdifferentiate into fibroblasts and contribute to cardiac fibrosis. It is one aim of this proposal to study cardiac fibrosis in mice with genetically tagged endothelial cells, in which evidence could be provided that endothelial-mesenchymal-transition exists in the heart. A second aim is to investigate EMT of endothelial cells and its regulation in vitro.